Bispecific antibodies, or bispecific binding agents in general, are unique in the sense that they can bind simultaneously to two different epitopes on one antigen or to two different antigens. This property enables the development of novel therapeutic and diagnostic strategies that are not possible with conventional monoclonal antibodies. A large panel of bispecific dual binders, e.g. of bispecific antibody formats has been developed and reflects the strong scientific as well as commercial interest in these molecules.
Monoclonal antibodies (mAbs), being directed towards single epitopes on the antigen, usually bind with affinities which are less than the avidity of polyclonal antisera. However, certain pairs of mAbs directed towards different epitopes on the same antigen can bind that antigen more effectively and with an avidity greater than the sum of the affinities of the corresponding individual mAb alone.
However, the avidity constants for synergizing pairs of mAb or for a chemically cross-linked bispecific F(ab′)2 is generally only up to 15 times greater than the affinity constants for the individual mAb, which is significantly less than the theoretical avidity expected for ideal combination between the reactants (Cheong, H. S., et al., Biochem. Biophys. Res. Commun. 173 (1990) 795-800). One reason for this might be that the individual epitope/paratope interactions involved in a synergistic binding (resulting in a high avidity) must be orientated in a particular way relative to each other for optimal synergy.